TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35748	107467;107468;107469	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
N2AB	34107	102544;102545;102546	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
N2A	33180	99763;99764;99765	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
N2B	26683	80272;80273;80274	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
Novex-1	26808	80647;80648;80649	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
Novex-2	26875	80848;80849;80850	chr2:178528409;178528408;178528407	chr2:179393136;179393135;179393134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-168
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1068
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/A	None	None	0.024	N	0.463	0.318	0.515149029962	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43968E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.2562	likely_benign	0.2652	benign	-1.571	Destabilizing	0.024	N	0.463	neutral	N	0.486980538	None	None	N
V/C	0.694	likely_pathogenic	0.6789	pathogenic	-1.478	Destabilizing	0.628	D	0.639	neutral	None	None	None	None	N
V/D	0.5684	likely_pathogenic	0.5331	ambiguous	-0.956	Destabilizing	0.295	N	0.678	prob.neutral	D	0.531560821	None	None	N
V/E	0.5	ambiguous	0.471	ambiguous	-0.879	Destabilizing	0.356	N	0.675	prob.neutral	None	None	None	None	N
V/F	0.1348	likely_benign	0.1185	benign	-1.122	Destabilizing	0.055	N	0.635	neutral	N	0.467277269	None	None	N
V/G	0.3608	ambiguous	0.3686	ambiguous	-1.962	Destabilizing	0.106	N	0.683	prob.neutral	N	0.496120096	None	None	N
V/H	0.5998	likely_pathogenic	0.5507	ambiguous	-1.54	Destabilizing	0.864	D	0.647	neutral	None	None	None	None	N
V/I	0.0584	likely_benign	0.0577	benign	-0.569	Destabilizing	None	N	0.153	neutral	N	0.462967528	None	None	N
V/K	0.4864	ambiguous	0.4528	ambiguous	-1.158	Destabilizing	0.072	N	0.661	neutral	None	None	None	None	N
V/L	0.1473	likely_benign	0.1411	benign	-0.569	Destabilizing	None	N	0.154	neutral	N	0.495925308	None	None	N
V/M	0.1164	likely_benign	0.1154	benign	-0.701	Destabilizing	0.003	N	0.23	neutral	None	None	None	None	N
V/N	0.3435	ambiguous	0.3211	benign	-1.106	Destabilizing	0.628	D	0.689	prob.neutral	None	None	None	None	N
V/P	0.8868	likely_pathogenic	0.8839	pathogenic	-0.869	Destabilizing	0.628	D	0.656	neutral	None	None	None	None	N
V/Q	0.4715	ambiguous	0.4351	ambiguous	-1.133	Destabilizing	0.356	N	0.665	neutral	None	None	None	None	N
V/R	0.4077	ambiguous	0.3664	ambiguous	-0.885	Destabilizing	0.356	N	0.681	prob.neutral	None	None	None	None	N
V/S	0.2982	likely_benign	0.3001	benign	-1.825	Destabilizing	0.136	N	0.629	neutral	None	None	None	None	N
V/T	0.2081	likely_benign	0.2093	benign	-1.61	Destabilizing	0.072	N	0.536	neutral	None	None	None	None	N
V/W	0.7559	likely_pathogenic	0.7357	pathogenic	-1.324	Destabilizing	0.864	D	0.663	neutral	None	None	None	None	N
V/Y	0.4509	ambiguous	0.4105	ambiguous	-0.989	Destabilizing	0.356	N	0.672	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.